Background: Trilateral retinoblastoma is a well recognized, although rare, syndrome. Most of the reported cases have involved a family history of retinoblastoma (RB) and the disease is almost always fatal. The authors chose to investigate the cases of trilateral retinoblastoma occurring in the West Midlands, a region of the United Kingdom with an increasing incidence of bilateral sporadic RB., Methods: Five patients with trilateral retinoblastoma (including two were previously reported), diagnosed in 146 consecutive patients with RB in the West Midlands Health Authority Region between 1957 and 1994, are presented (an incidence of 3%). Their clinical presentation, treatment, and outcome are described., Results: There were 4 patients with pineoblastoma, only one of whom had a positive family history. The mean age at diagnosis of RB and 6 months, whereas the patients with pineoblastoma were diagnosed at a mean age of 2 years 8 months. The tumors were not evident on the initial computed tomography scans. One child presented with a calcified suprasellar mass 13 months before the bilateral sporadic RB was identified. Death occurred within 1 month of diagnosis of the intracranial tumor in 3 patients who did not receive any treatment. In the other 2 patients who were treated, death occurred at 15 months and 2 years 7 months, respectively, after diagnosis of intracranial tumor., Conclusions: Early diagnosis with regular neuro-imaging and more aggressive treatment may improve prognosis in patients with RB and an intracranial tumor.